Incidence Of Primary Aldosteronism Research Articles

Incidence of Primary Aldosteronism in Patients with Hypokalemia (IPAHK+): Study Design and Baseline Characteristics.

Hypokalemia plays a central role for case finding, course, treatment decision, and prognosis of patients with primary aldosteronism. However, to date there is a lack of high-level evidence about the incidence of primary aldosteronism in hypokalemic patients. The IPAHK+study is an epidemiological, cross-sectional, monocentric study to provide evidence on the incidence of PA in a hypokalemic population. The aim of the current analysis was to describe the baseline characteristics of the first 100 patients eligible for study inclusion. The recruitment of patients with hypokalemia (≤3 mmol/l) is carried out continuously on a referral-basis by the central laboratory of the University Hospital Zurich through an automated suitability testing and data delivery system. The careful evaluation of the first 100 reported patients was based on the available reporting system. Out of 28 140 screened patients, 222 (0.79%) were identified with a serum potassium value of≤3 mmol/l (mean 2.89±0.02 mmol/l). Mean potassium levels were slightly lower in non-hypertensive subjects compared to hypertensive subjects (mean difference 0.07 mmol/l, p=0.033), while no significant difference was found between the sexes and patients with and without the diagnosis of primary aldosteronism, atrial fibrillation, or the use of diuretics. The incidence of PA was 4% in the total population studied and 7.5% in the subgroup of hypertensive patients. In conclusion, the continuous enrollment of patients from the IPHAK+hypokalemia registry into the IPAHK+trial will provide evidence about the actual incidence of primary aldosteronism in a hypokalemic outpatient population.

Increasing incidence of primary aldosteronism – yet an underdiagnosed disorder

Increasing incidence of primary aldosteronism – yet an underdiagnosed disorder

Hypokalemia and the Prevalence of Primary Aldosteronism.

Hypokalemia is closely linked with the pathophysiology of primary aldosteronism (PA). Although hypokalemic PA is less common than the normokalemic course of the disease, hypokalemia is of particular importance for the manifestation and development of comorbidities. Specifically, a growing body of evidence demonstrates that hypokalemia in PA patients is associated with a more severe disease course regarding cardiovascular and metabolic morbidity and mortality. It is also well appreciated that low potassium levels per se can promote or exacerbate hypertension. The spectrum of hypokalemia-related symptoms ranges from asymptomatic courses to life-threatening conditions. Hypokalemia is found in 9-37% of all cases of PA with a predominance in patients with aldosterone producing adenoma. Conversely, hypokalemia resolves in almost 100% of cases after both, specific medical or surgical treatment of the disease. However, to date, high-level evidence about the prevalence of primary aldosteronism in a hypokalemic population is missing. Epidemiological data are expected from the recently launched IPAHK+study ("Incidence of Primary Aldosteronism in Patients with Hypokalemia").

Primary aldosteronism associated with subclinical Cushing syndrome.

Recently, it has been reported that the incidence of primary aldosteronism (PA) among patients with hypertension is much more frequent than previously reported. In the present study, we investigated the frequency and features of PA associated with subclinical Cushing syndrome (SCS). Subjects included consecutive patients (no.=39) who were diagnosed as PA and performed adrenal venous sampling between 2003 and 2011 in our institute. In 39 subjects who were diagnosed as PA, 29 patients were operated and 5 cases (12.8%) showed no suppression in low-dose dexamethasone suppression test. Four cases of them were demonstrated to be associated with SCS, and one was associated with overt Cushing syndrome (CS). Post-operatively, 3 cases received replacement therapy of hydrocortisone, while others did not. Pathological findings indicated the diagnosis of aldosterone-producing adenoma in 4 cases associated with SCS, and of idiopathic hyperaldosteronismin in one case associated with overt CS. In all 5 cases, immunohistochemical analysis demonstrated the immunoreactivities of both 3βHSD and P450c17 in the adrenocortical tumors, the marked cortical atrophy in the zona fasciculata and reticularis, the decreased dehydroepiandrosterone sulfotransferase expression, and suppression of hypothalamo- pituitary-adrenal axis indicating the autonomous secretion of cortisol from the tumor. The present study suggests that PA is frequently associated with SCS with prevalence of more than 10%, justifying the routine examinations for SCS in PA cases.

Increasing Incidence of Primary Aldosteronism in Patients Investigated for Resistant Hypertension: An Observational Study from a Nephrology Unit

Introduction: Primary Aldosteronism (PA) is a secondary form of hypertension characterized by an autonomous and inappropriately high production of aldosterone. Its prevalence is 5-12% and the two main subtypes are the Bilateral Adrenal Hyperplasia (BAH) and the Aldosterone-Producing Adenoma (APA). In this study, we report the results of an evalutation of some patients diagnosed with PA in a Nephrology Unit between 1987-2011. Patients and methods: As much as 54 patients were screened for PA by measuring Plasma Aldosterone Concentration (PAC) and Plasma Renin Activity (PRA), and by calculating the aldosterone/renin ratio (ARR). Confirmation tests were performed on 47 patients with PAC ≥ 15 ng/dL and ARR ≥ 40. Subtype diagnosing was possible through adrenal CT scan, scintigraphy and adrenal venous sampling. Results: As much as 31 patients were diagnosed with PA. In 17 of them, the concordance of CT, scintigraphy and AVS findings made it possible to determine the subtype diagnosis: BAH in 10 and APA in 7 patients. Conclusions: Our results confirm the increasing frequency of diagnosis of PA among patients investigated for resistant hypertension. Early detection of PA in nephrological settings is important because of the relationship between aldosterone and kidney function.

Aldosteronism and Resistant Hypertension

Resistant hypertension (RHTN) is defined as blood pressure (BP) that remains uncontrolled in spite of intake of ≥3 antihypertensive medications, ideally prescribed at optimal doses and one of which is a diuretic. The incidence of primary aldosteronism (PA) in patients with RHTN is estimated in prospective studies to be 14 to 23%, which is higher than in the general hypertensive population. Patients with PA are at an increased cardiovascular risk, as shown by higher rates of stroke, myocardial infarction, and arrhythmias compared to hypertensive individuals without PA. Likewise, RHTN is associated with adverse cardiovascular outcomes, and the contribution of PA to this increased risk is undetermined. Similar to PA, obstructive sleep apnea (OSA) is closely associated with RHTN, and a causal link between PA, OSA, and RHTN remains to be elucidated. The addition of MR antagonists to the antihypertensive regimen in patients with RHTN produces a profound BP-lowering effect, and this effect is seen in patients with or without biochemical evidence of PA, highlighting the role of relative aldosterone excess in driving treatment resistance in this group of patients.

Antihypertensive efficacy of spironolactone: what about sex?

We read with interest the paper of Parthasarathy et al. [1], investigating the blood pressure (BP) response to two different diuretics [a mineralocorticoid receptor antagonist (MRA) and a thiazide diuretic] in patients subdivided, according to aldosterone-to-renin ratio (ARR) value, in high and low ARR group, respectively. Given the high incidence of primary aldosteronism and the widely recognized adverse effects of aldosterone on cardiovascular system, further research on MRA use in hypertensive patients is warranted.

Amelioration of metabolic acidosis in patients with low GFR reduced kidney endothelin production and kidney injury, and better preserved GFR

Metabolic acidosis often accompanies low glomerular filtration rate and induces secretion of endothelin, which in turn might mediate kidney injury. Here we tested whether treatment of metabolic acidosis in patients with low glomerular filtration rate reduced the progression of kidney disease. Fifty-nine patients with hypertensive nephropathy and metabolic acidosis had their blood pressure reduced with regimens that included angiotensin-converting enzyme inhibition. Thirty patients were then prescribed sodium citrate, and the remaining 29, unable or unwilling to take sodium citrate, served as controls. All were followed for 24 months with maintenance of their blood pressure reduction. Urine endothelin-1 excretion, a surrogate of kidney endothelin production, and N-acetyl-beta-D-glucosaminidase, a marker of kidney tubulointerstitial injury, were each significantly lower, while the rate of estimated glomerular filtration rate decline was significantly slower. The estimated glomerular filtration rate was statistically higher after 24 months of sodium citrate treatment compared to the control group. Hence it appears that sodium citrate is an effective kidney-protective adjunct to blood pressure reduction and angiotensin-converting enzyme inhibition.

Salivary Aldosterone as a Diagnostic Aid in Primary Aldosteronism

Recent evidence demonstrates an increased incidence of primary aldosteronism (PA) in approximately 10% of the hypertensive population, making noninvasive and simple screening methods necessary. The aim of the present study was to apply a time-resolved fluorescence immunoassay for the measurement of aldosterone in saliva and the establishment of a cut-off to identify patients with a high likelihood for PA requiring subsequent screening with the aldosterone to renin ratio. Saliva was collected (AM and PM) to ascertain an optimum time with best discriminating power between healthy and disease states. Plasma aldosterone, after overnight recumbency and 4 h later, was collected for posture testing. The participants included 53 PA patients (aged 14-78), 54 with essential hypertension (EH, aged 19-82), and 38 healthy volunteers (aged 19-56). Saliva aldosterone (SA) (median, 25-75(th)%) in PA was found at 90 pg/ml (61-139) compared to 53 pg/ml (40-85) in EH, with discrimination between PA versus EHs best in the morning (cutoff: 81 pg/ml, 77% sensitivity, 82% specificity). Saliva aldosterone decreases throughout the day in patients with adenomas [APA AM: 123 pg/ml (92-213) vs. PM: 79 pg/ml (41-116)], but not in those with bilateral hyperplasia [BAH AM: 85 pg/ml (59-115)] vs. pm 69 pg/ml (57-114). Morning SA alone allows discrimination between PA and controls, though with significant overlap against EHs, leading to a high number of false positives. More promising is the use of diurnal variation in SA in distinguishing between APA and BAH. The decline in SA seen in patients with APA presents a more constant finding compared to posture testing, which fails to correctly classify a large number of patients.

Mineralocorticoid receptors and pathophysiological roles for aldosterone in the cardiovascular system.

For almost 40 years since its discovery in 1953, the mineralocorticoid hormone, aldosterone, was considered to affect blood volume, and thus blood pressure, by its action to retain sodium at epithelial tissues. Over the past decade, direct effects of aldosterone on the heart and blood vessels, and on the cerebral control of blood pressure, have been established in experimental animals. Simultaneously, the incidence of primary aldosteronism in essential hypertension is now acknowledged to be 10-20%, rather than <or= 1%, underscoring a previously unrecognized role for aldosterone in hypertension. The 30% improvement in mortality (and 35% in morbidity) seen in the RALES trial with the addition of low-dose spironolactone to best practice therapy in moderate to severe heart failure, similarly points to an unrecognized role for aldosterone in the pathophysiology of heart failure. Currently, both experimental and clinical studies are directed towards establishing the mechanisms involved in these pathophysiological effects of aldosterone in the cardiovascular system, and of the role of mineralocorticoid receptor antagonists in offsetting or blocking such effects. A brief account of the current state of these mechanisms in at a cellular and tissue level forms the basis of this review.

Caution About the Overdiagnosis of Primary Aldosteronism

Caution About the Overdiagnosis of Primary Aldosteronism

Primary aldosteronism and its variants.

Time for primary reviews 33 days. Primary aldosteronism is an adrenal abnormality in which there is an excessive production of aldosterone above that required for electrolyte homeostasis which is not driven by known stimulators of aldosterone secretion, although these may retain some degree of modulatory activity on aldosterone secretion. In the early years following the description of primary aldosteronism, the etiology was ascribed to the autonomous production of aldosterone by an adrenal adenoma for which surgical treatment resulted in the resolution of the hypokalemia and cure or improvement of the hypertension in many cases [1]. At this time the possibility of aldosteronism due to adrenal hyperplasia was not recognized. The traditional clinical picture was characterized by salt-sensitive hypertension associated with hypokalemia and suppression of renin secretion [1]. A major emphasis in the selection of patients for consideration for diagnostic procedures for primary aldosteronism was the presence of spontaneous or easily-induced hypokalemia, resulting in an underestimation of the incidence of primary aldosteronism [2, 3]. Once identified, normokalemic primary aldosteronism was found to be common; many patients with primary aldosteronism are normokalemic most of the time [2, 4, 5]. The widespread commercial availability of methods to easily measure aldosterone and plasma renin activity (PRA) allowed the screening of patients with essential hypertension, irrespective of the serum potassium, and has led to the recognition that primary aldosteronism has higher prevalence than previously recognized [2, 6, 7]. Various stimulatory and localization maneuvers have led to the recognition that there are several types of primary aldosteronism with variable response to surgery [8–10]. The purpose of this mini review is to succinctly address the issues of prevalence, sub types and pathogenesis of primary aldosteronism so that appropriate therapy may be chosen. Curable forms of hypertension have a special appeal for …

Evidence that primary aldosteronism may not be uncommon: 12% incidence among antihypertensive drug trial volunteers.

1. Six (12%) out of 52 respondents to newspaper advertisements for antihypertensive drug trials had elevated aldosterone to renin ratio, confirmed by repeated measurement. 2. Failure to suppress aldosterone with fludrocortisone acetate administration and oral salt loading confirmed the presence of primary aldosteronism in all six patients. 3. Two of the six patients have already had aldosterone-producing adenomas removed, one has commenced spironolactone, and one has an adrenal mass on computerized tomography but investigation is incomplete. 4. None of the six patients with primary aldosteronism had unprovoked hypokalaemia. 5. Plasma aldosterone levels did not distinguish those patients with subsequently proven primary aldosteronism from the others. Plasma renin activity (PRA) was a better discriminator, but not as good as the aldosterone to renin ratio. 6. The incidence of primary aldosteronism is probably much higher than the 1% currently quoted in texts, with earlier, normokalaemic forms accounting for the majority of cases.

Renin and aldosterone in essential hypertension.

1. The renin-aldosterone system was studied in seventy-one selected hypertensive patients. Nine (13%) were diagnosed as having primary aldosteronism. Of the twenty-three patients who presented with a history of unprovoked hypokalaemia, the incidence of primary aldosteronism was 40%. 2. Renin and aldosterone responses to the combined stimuli of a low sodium diet and the upright posture were suppressed in patients with essential hypertension. There was no evidence that the suppression was due to abnormal adrenal function, sympathetic neuropathy, or the level of the blood pressure. The mechanism of the suppressed plasma renin activity response and its significance in the pathogenesis of hypertension are unknown.

A Concluding Response

I am delighted to have this opportunity to comment upon "Incidence of Primary Aldosteronism" by Dr. Kaplan. I shall make no attempt at a point by point rebuttal of the same argument that Dr. Kaplan has raised on two previous occasions. 1,2 My purpose in responding is to put in proper perspective the entire content of Dr. Kaplan's comment in the hope that the subject will not be raised again. First, I am gratified that the writer sees fit to state "regardless of its incidence, the recognition of normokalemic primary aldosteronism as a masquerade of 'essential' hypertension is a discovery of great importance," and that "the availability of better diagnostic procedures and the insights into our understanding of the role of aldosterone in hypertension are, in themselves, major advances which have resulted from the stimulus provided by Dr. Conn and his co-workers." If these statements are acceptable to others

Commentary on incidence of primary aldosteronism: current estimations based on objective data

Commentary on incidence of primary aldosteronism: current estimations based on objective data

Commentary on Incidence of Primary Aldosteronism

In addition to the study reported on pages 141-146, submitted to the Archives the following essay covering a discussion of the incidence of aldosterone-producing tumors in patients presenting with the clinical picture of normokalemic hypertension. We sent the essay on to Dr. Conn and invited his comments. He, in turn, sent along a study of his own, summarizing his latest experience (pages 113-123), and also his response to Dr. Kaplan's critique which follows this article.—Ed.

Study on the renin-angiotensin-aldosterone system. Effects of sodium restriction and postural changes on plasma renin activity and fluctuation in urinary aldosterone

Recent observations have demonstrated that the renin-angiotensin system is concerned with the regulation of aldosterone secretion and blood pressure, and measurement of plasma renin activity (PRA) can contribute to a great extent to the evaluation of patients with hypertension. It has been already certified that PRA is significantly and extremely suppressed in patients with primary aldosteronism. The following experiments were studied about the most effective diagnostics of primary aldosteronism, the optimum and convenient conditions for measuring PRA in sodium restriction and upright position and furthermore the incidence of primary aldosteronism among patients with essential hypertension, and evaluation of the renin-angiotensin-aldosterone system in patients with various kinds of hypertension. Materials and Methods. 76 patients with essential hypertension 4 with renovascular hypertension, 10 with primary aldosteronism and 9 normal subjects were examined in these studies. Each subject was fed on a diet containing various amounts of sodium (300mEq, 130mEq, 30-40mEq) for at least three days prior to study. A sample of peripheral venous blood was obtained in the morning after overnight recumbency and after two to four hours of upright position plus thiazide administratoin (Fig. 1). PRA was measured by BOUCHER'S method and urinary aldosterone was determined by blue tetrazolium coloration (or double isotope derivative method) utilizing our new systems of thin layer chromatography instead of paper chromatography because of the economy of time and cost without the sacrifice of accuracy (Fig.2, 3). R Results: Recumbent PRA was a little more increased in a group taking 130 mEq/day sodium than 300 mEq/day sodium and more effectively increased in a severe restriction of sodium intake (30-40 mEq) and most definitely increased on a low sodium diet combined with upright ambulation. Each subject should be fed on a low sodium diet for at least four days to examine PRA (Table I and II). The study on an optimum time for measuring PRA increase in upright ambulation showed a maximum increase after 180-240 min as compared with values obtained after 60 minutes, but usually showed the almost sufficient values after 120 minutes (Fig. 5).

Plasma Renin Activity in Healthy Subjects and Patients With Hypertension

RECENT observations have demonstrated that measurements of plasma renin activity (PRA) can contribute importantly to the evaluation of patients with hypertension. 1-9 This procedure appears particularly useful to the evaluation of patients whose hypertension is secondary to either renovascular disease or primary aldosteronism. Plasma renin activity has been said to be elevated in patients with renovascular hypertension, 2-6,9 and suppressed or low in patients with hypertension due to primary aldosteronism. 7,8,10 In fact, Conn and his colleagues have suggested that the finding of reduced or suppressed PRA provides strong evidence for underlying primary aldosteronism even in the presence of normokalemia 8,10 and that the incidence of primary aldosteronism may be as high as 20% among patients with benign essential hypertension. 7 Despite its apparent usefulness and potential importance, the bio-assay of PRA has not yet enjoyed widespread use because of the complexity or qualitative nature of most existing methods. 191115 There is a real need for

Plasma renin activity in healthy subjects and patients with hypertension. Preliminary experience with a rapid and quantitative bio-assay

RECENT observations have demonstrated that measurements of plasma renin activity (PRA) can contribute importantly to the evaluation of patients with hypertension.^1-9This procedure appears particularly useful to the evaluation of patients whose hypertension is secondary to either renovascular disease or primary aldosteronism. Plasma renin activity has been said to be elevated in patients with renovascular hypertension,^2-6,9and "suppressed" or low in patients with hypertension due to primary aldosteronism.^7,8,10In fact, Conn and his colleagues have suggested that the finding of reduced or "suppressed" PRA provides strong evidence for underlying primary aldosteronism even in the presence of normokalemia^8,10and that the incidence of primary aldosteronism may be as high as 20% among patients with "benign essential" hypertension.⁷ Despite its apparent usefulness and potential importance, the bio-assay of PRA has not yet enjoyed widespread use because of the complexity or qualitative nature of most existing methods.¹⁹¹¹¹⁵There is a real need for